Cadmium (Cd) and tributyltin (TBT) are common contaminants of marine and freshwater ecosystems, and can induce the formation of reactive oxygen species (ROS). These ROS can, in turn, cause oxidative stress. In the present study, we investigated time-related effects of Cd (0.05 and 0.1 ppm) and TBT (5 and 10 ppb) treatment on antioxidant enzyme activity, i.e., the activity of superoxide dismutase (SOD) and catalase (CAT) in the gills and digestive glands of the ark shell, Scapharca broughtonii. In addition, hydrogen peroxide ($H_2O_2$) concentrations, lysozyme activity, and glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were measured in the hemolymph. We found that Cd and TBT treatment significantly increased antioxidant enzyme mRNA expression and activity in the digestive glands and gills in a time-dependent manner. In response to the Cd and TBT treatments, antioxidant enzymes mRNA expression and activity increased up to day 5 in the digestive glands and then decreased by day 7. In the gills, antioxidant enzymes mRNA expression and activity increased up to day 3 and then decreased by day 5. Likewise, $H_2O_2$ concentrations significantly increased up to day 5 and then decreased by day 7. Finally, lysozyme activity decreased during the experimental period, whereas GOT and GPT levels were significantly increased in a time-dependent manner. These results suggest that antioxidant enzymes play an important role in decreasing ROS levels and oxidative stress in ark shells exposed to Cd and TBT.